Q8J025 (APCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein APCDD1

Alternative name(s):
Adenomatosis polyposis coli down-regulated 1 protein

Gene names

Name:	APCDD1
Synonyms:	DRAPC1
ORF Names:	FP7019

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	514 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin. May act via its interaction with Wnt and LRP proteins. May play a role in colorectal tumorigenesis. Ref.1 Ref.5
Subunit structure	Homodimer. Interacts with LRP5 and WNT3A. Ref.5
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.5.
Tissue specificity	Abundantly expressed in heart, pancreas, prostate and ovary. Moderately expressed in lung, liver, kidney, spleen, thymus, colon and peripheral lymphocytes. Abundantly expressed in both the epidermal and dermal compartments of the hair follicle. Present in scalp skin Highly expressed in the hair follicle dermal papilla, the matrix, and the hair shaft (at protein level). Ref.1 Ref.5
Induction	Target gene of the Wnt/Beta-catenin pathway, transcriptionally regulated by the CTNNB1/TF7L2 complex. Ref.1
Post-translational modification	N-Glycosylated. Ref.5
Involvement in disease	Defects in APCDD1 are a cause of hypotrichosis type 1 (HYPT1) [MIM:605389]. A rare form of non-syndromic hereditary hypotrichosis without characteristic hair shaft anomalies. Affected individuals typically show normal hair at birth, but hair loss and thinning of the hair shaft start during early childhood and progress with age. Ref.5
Sequence similarities	Belongs to the APCDD1 family.
Sequence caution	The sequence AAQ04816.1 differs from that shown. Reason: Frameshift at position 133. The sequence BAG64192.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hypotrichosis
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW hair follicle development Inferred from mutant phenotype Ref.5. Source: UniProtKB negative regulation of Wnt receptor signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB
Cellular component	integral to plasma membrane Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	Wnt-protein binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8J025-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8J025-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKRRCSCGGGGGHCSSERRRTRPEAEGRARAQLPGHQIGARRAGGPRAGLEM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 514	488	Protein APCDD1		PRO_0000227520
Regions
	Topological domain	27 – 492	466	Extracellular Potential
	Transmembrane	493 – 512	20	Helical; Potential
	Topological domain	513 – 514	2	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	100	1	N-linked (GlcNAc...) Potential
	Glycosylation	168	1	N-linked (GlcNAc...) Potential
	Glycosylation	319	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1	1	M → MKRRCSCGGGGGHCSSERRR TRPEAEGRARAQLPGHQIGA RRAGGPRAGLEM in isoform 2.		VSP_039542
	Natural variant	9	1	L → R in HYPT1; dominant-negative mutant that perturbs the translational processing from the endoplasmic reticulum to the plasma membrane. Ref.5		VAR_063497
	Natural variant	150	1	V → I. Corresponds to variant rs3748415 [ dbSNP | Ensembl ].		VAR_050667

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 75DA7B8B38E3FFE5	FASTA	514	58,797
	10 20 30 40 50 60 MSWPRRLLLR YLFPALLLHG LGEGSALLHP DSRSHPRSLE KSAWRAFKES QCHHMLKHLH 70 80 90 100 110 120 NGARITVQMP PTIEGHWVST GCEVRSGPEF ITRSYRFYHN NTFKAYQFYY GSNRCTNPTY 130 140 150 160 170 180 TLIIRGKIRL RQASWIIRGG TEADYQLHNV QVICHTEAVA EKLGQQVNRT CPGFLADGGP 190 200 210 220 230 240 WVQDVAYDLW REENGCECTK AVNFAMHELQ LIRVEKQYLH HNLDHLVEEL FLGDIHTDAT 250 260 270 280 290 300 QRMFYRPSSY QPPLQNAKNH DHACIACRII YRSDEHHPPI LPPKADLTIG LHGEWVSQRC 310 320 330 340 350 360 EVRPEVLFLT RHFIFHDNNN TWEGHYYHYS DPVCKHPTFS IYARGRYSRG VLSSRVMGGT 370 380 390 400 410 420 EFVFKVNHMK VTPMDAATAS LLNVFNGNEC GAEGSWQVGI QQDVTHTNGC VALGIKLPHT 430 440 450 460 470 480 EYEIFKMEQD ARGRYLLFNG QRPSDGSSPD RPEKRATSYQ MPLVQCASSS PRAEDLAEDS 490 500 510 GSSLYGRAPG RHTWSLLLAA LACLVPLLHW NIRR
	Isoform 2 [UniParc]. Checksum: 40C79B378480EAAF	FASTA	565	64,178
	10 20 30 40 50 60 MKRRCSCGGG GGHCSSERRR TRPEAEGRAR AQLPGHQIGA RRAGGPRAGL EMSWPRRLLL 70 80 90 100 110 120 RYLFPALLLH GLGEGSALLH PDSRSHPRSL EKSAWRAFKE SQCHHMLKHL HNGARITVQM 130 140 150 160 170 180 PPTIEGHWVS TGCEVRSGPE FITRSYRFYH NNTFKAYQFY YGSNRCTNPT YTLIIRGKIR 190 200 210 220 230 240 LRQASWIIRG GTEADYQLHN VQVICHTEAV AEKLGQQVNR TCPGFLADGG PWVQDVAYDL 250 260 270 280 290 300 WREENGCECT KAVNFAMHEL QLIRVEKQYL HHNLDHLVEE LFLGDIHTDA TQRMFYRPSS 310 320 330 340 350 360 YQPPLQNAKN HDHACIACRI IYRSDEHHPP ILPPKADLTI GLHGEWVSQR CEVRPEVLFL 370 380 390 400 410 420 TRHFIFHDNN NTWEGHYYHY SDPVCKHPTF SIYARGRYSR GVLSSRVMGG TEFVFKVNHM 430 440 450 460 470 480 KVTPMDAATA SLLNVFNGNE CGAEGSWQVG IQQDVTHTNG CVALGIKLPH TEYEIFKMEQ 490 500 510 520 530 540 DARGRYLLFN GQRPSDGSSP DRPEKRATSY QMPLVQCASS SPRAEDLAED SGSSLYGRAP 550 560 GRHTWSLLLA ALACLVPLLH WNIRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a novel human gene, APCDD1, as a direct target of the b-catenin/T-cell factor 4 complex with probable involvement in colorectal carcinogenesis." Takahashi M., Fujita M., Furukawa Y., Hamamoto R., Shimokawa T., Miwa N., Ogawa M., Nakamura Y. Cancer Res. 62:5651-5656(2002) [PubMed: 12384519] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INDUCTION. Tissue: Colon.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Neuroepithelioma and Thymus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Ovary.
[4]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-514.
[5]	"APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex." Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A., Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A., Christiano A.M. Nature 464:1043-1047(2010) [PubMed: 20393562] [Abstract] Cited for: VARIANT HYPT1 ARG-9, CHARACTERIZATION OF VARIANT HYPT1 ARG-9, GLYCOSYLATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT, INTERACTION WITH LRP5 AND WNT3A.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB056722 mRNA. Translation: BAC15563.1. AB104887 mRNA. Translation: BAC65165.1. AK300743 mRNA. Translation: BAG62412.1. AK303076 mRNA. Translation: BAG64192.1. Different initiation. BC053324 mRNA. Translation: AAH53324.1. AF461902 mRNA. Translation: AAQ04816.1. Frameshift.
IPI	IPI00216332. IPI00939369.
RefSeq	NP_694545.1. NM_153000.4.
UniGene	Hs.293274.
3D structure databases
ProteinModelPortal	Q8J025.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-56190N.
IntAct	Q8J025. 1 interaction.
STRING	Q8J025.
PTM databases
PhosphoSite	Q8J025.
Polymorphism databases
DMDM	74728445.
Proteomic databases
PRIDE	Q8J025.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355285; ENSP00000347433; ENSG00000154856. ENST00000423585; ENSP00000404930; ENSG00000154856.
GeneID	147495.
KEGG	hsa:147495.
UCSC	uc002kom.2. human.
Organism-specific databases
CTD	147495.
GeneCards	GC18P010444.
H-InvDB	HIX0014332.
HGNC	HGNC:15718. APCDD1.
HPA	HPA014468.
MIM	605389. phenotype. 607479. gene.
neXtProt	NX_Q8J025.
Orphanet	55654. Hypotrichosis simplex.
PharmGKB	PA24876.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08479.
GeneTree	ENSGT00390000000925.
HOVERGEN	HBG060356.
InParanoid	Q8J025.
OMA	CHTEAVA.
OrthoDB	EOG4548ZM.
PhylomeDB	Q8J025.
Gene expression databases
ArrayExpress	Q8J025.
Bgee	Q8J025.
CleanEx	HS_APCDD1.
Genevestigator	Q8J025.
GermOnline	ENSG00000154856. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	85626.
SOURCE	Search...

Entry information

Entry name

APCD1_HUMAN

Accession

Primary (citable) accession number: Q8J025
Secondary accession number(s): B4DUQ0, B4DZT0, Q71M25

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	March 1, 2003
Last modified:	December 14, 2011
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.